RNA metabolism is dynamically orchestrated by RNA-binding proteins (RBPs) in different
subcellular spaces. Aberrant regulation of the subcellular RNA-protein interactions leads
to severe diseases, such as neural degenerations and cancers. Understanding the precise
spatiotemporal dynamics of RBPs and their interacting networks in the steady state and
upon perturbation is key to deciphering the cell function. We present the coRIC
(compartmentalized RNA Interactome Capture) map, an experimental resource and
analytical pipeline to study the subcellular dynamics of RBPs through multimodal dataset
integration and machine learning. coRIC map successfully identified 1,768 RBPs, including
previously underestimated RBPs, spanning 14 major subcellular regions. This map offered
us the opportunity to delineate subcellular RBP features, their intermolecular and
intercompartmental relationships. We have also defined the hierarchy of RBP complexes
at multiple scales across the cell, uncovering previously unknown functions of multiple
RBPs, such as IGF2BP1. Application of coRIC under the perturbations of DNA damage
and ALS-related dipeptide repeats uncovered the cRBP dynamic changes in complex
composition and subcellular distribution. Our work provides a new reference for
systematically studying the subcellular RNA-protein interactions, which helps understand
the RBP regulatory networks in RNA biology and disease.
(Universitat Pompeu Fabra, 2024-11-06T14:26:44Z) Guo, Xiangpeng; Di Croce, Luciano; Esteban, Miguel A.; Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida
